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1.
J Assoc Physicians India ; 68(2): 18-22, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32009356

RESUMO

Background: Rheumatoid arthritis (RA) is a chronic inflammatory connective tissue disorder with wide spectrum of presentation from polyarthritis to multisystem involvement. Apart from bones, muscles and other soft tissues, Vitamin D receptors have been found on many immune cells and tissues. The most vital function of Vitamin D is calcium and phosphorus absorption but it can also act as an immune-modulator hormone, which can affects both innate and adaptive immune responses leading to autoimmune diseases. Objectives: To study the relationship of vitamin D insufficiency with disease activity and functional disability in patients of Rheumatoid Arthritis. Material and Methods: The present study was an observational, cross sectional study done in a tertiary care hospital in New Delhi, India. The inclusion criteria comprised of patients attending the inpatient (IPD) and outpatient department (OPD), age above 18 years and fulfilling 1987 American college of Rheumatology (ACR) criteria for RA. The exclusion criteria was patients suffering from any other connective tissue disorder (CTD) and patients who were taking vitamin D supplements for past 6 months. Thirty patients were enrolled in the study after satisfying inclusion and exclusion criteria and appropriate clinical data and blood sample were collected after informed consent. Joint examination were performed and swollen joint count (SJC), tender joint count (TJC), patient global assessment (PGA) and evaluator global assessment (EGA) scores were recorded. Disease activity using DAS28ESR, DAS28CRP and CDAI were calculated and disability index was assessed using Short Fries Health Assessment Questionnaire. Results: In our study mean vitamin D level was 18.93 ng/ml (S.D. 6.64 ng/ml). Mean DAS28 ESR was 4.57±1.48. Mean Disability Index was 0.52±0.89. All the study population had low Vitamin D level (100%), while 50% patients had vitamin D level in deficiency range (<20ng/ml). On analysis by student t-test, statistically higher PGA (p value 0.024) and Disability Index (p value < 0.001) in vitamin D deficient patients, compared to vitamin D insufficient patient group was observed, however there was no significant difference in disease activity between the groups. Conclusion: Low Vitamin D levels are common in Indian rheumatoid arthritis patients. Mean PGA significantly increased, and disability index significantly increased in Vitamin D deficient group compared to insufficient group suggesting vitamin D deficient patients poor wellbeing and more disability.


Assuntos
Artrite Reumatoide/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/metabolismo , Artrite Reumatoide/metabolismo , Estudos Transversais , Humanos , Índia/epidemiologia , Índice de Gravidade de Doença
3.
J Zoo Wildl Med ; 50(4): 751-757, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926504

RESUMO

Although biochemical analytes have typically been measured using serum or whole blood samples, an increasing number of assays are validated for measurement of analytes from dried blood spots (DBS) on filter paper. DBS techniques are minimally invasive, require only a small sample volume, and simplify processing, storage, and shipment of samples. These qualities make DBS-based assays ideal for sampling of wildlife species in both captive and field settings. In this study, a liquid chromatography-tandem mass spectrometry assay was evaluated for measurement of 25-hydroxyvitamin D in sloths. Paired serum and DBS samples were collected from nine healthy captive Hoffmann's two-toed sloths (Choloepus hoffmanni). Statistical analysis using Passing-Bablok regression analysis, Bland-Altman plots, and the Wilcoxon signed-rank tests found good agreement between 25-hydroxyvitamin D3 measurements in serum and DBS samples. Constant and proportional bias were absent. Results from this study support the use of DBS samples for the evaluation of vitamin D status in Hoffmann's two-toed sloths and provide a foundation for further studies to validate this technique.


Assuntos
Cromatografia Líquida/veterinária , Teste em Amostras de Sangue Seco/veterinária , Bichos-Preguiça/sangue , Espectrometria de Massas em Tandem/veterinária , Vitamina D/análogos & derivados , Animais , Animais de Zoológico , Teste em Amostras de Sangue Seco/métodos , Feminino , Vitamina D/sangue
4.
Medicine (Baltimore) ; 99(2): e18338, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914014

RESUMO

BACKGROUND: This study aims to explore the effectiveness of vitamin D for the management of adult patients with gingivitis. METHODS: We will perform a comprehensive search from the following electronic databases: Cochrane Library, PUBMED, EMBASE, AMED, CINAHL, WANGFANG, VIP, CBM, and China National Knowledge Infrastructure. All databases will be searched from their inceptions to the present without language limitation. We will also search for unpublished data to avoid missing more potential studies. Two authors will carry out study selection, data extraction, and methodological quality evaluation, respectively. RevMan 5.3 software will be utilized for statistical analysis. RESULTS: This study will summarize the up-to-date evidence about the anti-inflammatory effect of vitamin D for the management of adult patients with gingivitis through assessing modified gingival, gingival bleeding indices, inflammatory factors, plaque, quality of life, and any adverse events. CONCLUSION: This study may provide helpful evidence of vitamin D for the management of adult patients with gingivitis for clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019156561.


Assuntos
Gengivite/tratamento farmacológico , Gengivite/psicologia , Vitamina D/uso terapêutico , Adulto , China/epidemiologia , Gengivite/patologia , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Vitamina D/efeitos adversos
5.
Medicine (Baltimore) ; 99(2): e18661, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914053

RESUMO

RATIONALE: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by complex interactions between genetic and environmental factors. Recent studies suggest that Vitamin D3 or bumetanide therapy may improve the core symptoms of ASD in some individuals. However, there are no guidelines that provide clinicians with evidence-based treatment regimens for the use of these therapies in ASD. PATIENT CONCERNS: A 30-month-old female was referred to our department because she did not respond when her name was called. DIAGNOSIS: The patient was diagnosed with ASD by a team of autism experts according to American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. INTERVENTIONS: The patient was administered Vitamin D3 150,000 IU intramuscularly once a month and Vitamin D3 800 IU orally each day. After 6 months, Vitamin D3 supplementation was discontinued because of lack of effectiveness. Subsequently, oral bumetanide 0.5 mg twice daily was initiated. OUTCOMES: The patient's symptoms remained unchanged after 6 months of Vitamin D3 supplementation, and her serum 25 (OH) D levels had reached 52.4 ng/mL. At the parent's request, Vitamin D3 supplementation was discontinued because of lack of effectiveness. Thereafter, bumetanide was initiated. After 1 month of bumetanide, the patient's Childhood Autism Rating Scale score was 26, which is below the cutoff score for ASD. This case report suggests that Vitamin D3 and bumetanide target different mechanisms in the pathogenesis of ASD. LESSONS: Based on these observations, we discuss three possible scenarios for Vitamin D3 supplementation and propose that bumetanide should be initiated if Vitamin D3 supplementation is ineffective (identifier ChiCTR-CCC-13004498).


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Bumetanida/uso terapêutico , Vitamina D/uso terapêutico , Pré-Escolar , Suplementos Nutricionais , Feminino , Humanos
9.
Anticancer Res ; 40(1): 491-499, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892604

RESUMO

This article is a narrative review of recent epidemiological findings regarding ultraviolet-B (UVB) dose or exposure, serum 25-hydroxyvitamin D [25(OH)D] concentrations, vitamin D supplementation, and genetic variations in 25(OH)D concentration for incidence, survival, and mortality rates of overall and breast, colorectal, and prostate cancer. According to ecological studies, solar UVB doses are inversely correlated with incidence/mortality rates for about 20 cancer types. Observational studies support a role of higher 25(OH)D concentrations in reducing risk of breast and colorectal cancer incidence and mortality rates but, for prostate cancer, in increasing incidence rates while reducing mortality rates. Mendelian randomization studies offer little support for vitamin D in reducing cancer risk. Their primary limitation is that they only investigate small variations in genetically predicted 25(OH)D concentration near the population mean value. The secondary analyses from the VITAL clinical trial indicated significant reductions from 2000 IU/d of vitamin D3 supplementation in all-cancer incidence and mortality rates for selected subgroups. Thus, Hill's criteria for causality in a biological system are now largely satisfied for supporting the claim that vitamin D reduces the risk of cancer incidence and death.


Assuntos
Neoplasias/epidemiologia , Vitamina D/metabolismo , Suplementos Nutricionais , Humanos , Neoplasias/sangue , Neoplasias/mortalidade , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Vitamina D/sangue
10.
Anticancer Res ; 40(1): 511-518, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892606

RESUMO

BACKGROUND/AIM: This review examined the implications of using sunscreen photoprotection on 25(OH)D formation and determined the best photoprotective method to reduce the risk of skin cancer caused by ultraviolet radiation (UVR). Based on previous studies on 25(OH)D formation after use of different amounts of sunscreen and different doses of UVR for approximately one week to different body areas it is possible to estimate the amount of 25(OH)D formed after a week's holiday in Southern and Northern Europe. CONCLUSION: The best method of photoprotection by sunscreen is two consecutive applications before sun exposure, ensuring the use of sufficient amounts of sunscreen and minimizing the unprotected skin areas. The double application method simultaneously ensures a high photoprotection against erythema from sun exposure. Despite the use of sunscreen, the calculated serum 25(OH)D levels clearly increase to similar levels as those measured after sun vacations.


Assuntos
Protetores Solares/farmacologia , Vitamina D/análogos & derivados , Humanos , Pele/efeitos da radiação , Banho de Sol , Raios Ultravioleta , Vitamina D/metabolismo , Organização Mundial da Saúde
11.
Anticancer Res ; 40(1): 519-525, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892607

RESUMO

Due to latest advancements in the development of LC-MS/MS based assays and their applications in clinical chemistry, low abundant vitamin D metabolites can be detected at low concentration with high specificity. Consequently, there is a growing need for their synthesis as stable isotopically labeled compounds to be used as calibration and reference standards. Most commonly, ex chiral pool synthesis, starting with vitamin D2, and palladium(0) catalyzed coupling reactions are applied in vitamin D synthesis. By contrast, little is known so far regarding the application of cobalt complexes for this purpose. In fact, the Pausen-Khand reaction can be applied for the synthesis of a wide range of isotopically labeled vitamin D metabolites that are hardly accessible by other known methods. Applications, scope and limitations of the most recent vitamin D synthesis methods, with a particular focus on this new promising methodology using Co-complexes, are discussed.


Assuntos
Metaboloma , Vitamina D/biossíntese , Catálise , Humanos , Vitamina D/análogos & derivados , Vitamina D/química
12.
Anticancer Res ; 40(1): 527-534, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892608

RESUMO

Simple steatosis in non-alcoholic fatty liver disease (NAFLD) progresses to non-alcoholic steatohepatitis (NASH) when excessive fat accumulation is accompanied by ballooning, inflammation, and progressive hepatocellular injury. Due to the increasing global incidence of NAFLD/NASH and the lack of effective drugs, current treatment options are currently dominated by lifestyle interventions, including dietary and physical activity modifications. In this regard, vitamin D has received widespread attention in recent years. In line with its pleiotropic physiological effects, preclinical animal models and patient cohorts have demonstrated anti-inflammatory, anti-fibrotic and anti-proliferative effects of vitamin D on NAFLD and NASH. Several animal models have confirmed the association of vitamin D deficiency and NALFD/NASH severity in humans and revealed potential benefits of dietary vitamin D supplementation. These preclinical models also provide critical guidance to define the roles and therapeutic potential of vitamin D as well as its downstream functional mechanisms in the pathogenesis of fatty liver disease. This review summarizes vitamin D research in currently available animal models of fatty liver disease.


Assuntos
Fígado Gorduroso/metabolismo , Vitamina D/metabolismo , Animais , Pesquisa Biomédica , Modelos Animais de Doenças , Humanos
13.
Anticancer Res ; 40(1): 473-489, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892603

RESUMO

Melanoma is one of the most lethal types of skin cancer, with a poor prognosis once the disease enters metastasis. The efficacy of currently available treatment schemes for advanced melanomas is low, expensive, and burdened by significant side-effects. Therefore, there is a need to develop new treatment options. Skin cells are able to activate vitamin D via classical and non-classical pathways. Vitamin D derivatives have anticancer properties which promote differentiation and inhibit proliferation. The role of systemic vitamin D in patients with melanoma is unclear as epidemiological studies are not definitive. In contrast, experimental data have clearly shown that vitamin D and its derivatives have anti-melanoma properties. Furthermore, molecular and clinicopathological studies have demonstrated a correlation between defects in vitamin D signaling and progression of melanoma and disease outcome. Therefore, adequate vitamin D signaling can play a role in the treatment of melanoma.


Assuntos
Progressão da Doença , Melanoma/patologia , Melanoma/terapia , Vitamina D/metabolismo , Ensaios Clínicos como Assunto , Humanos , Raios Ultravioleta
14.
Anticancer Res ; 40(1): 535-543, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892609

RESUMO

BACKGROUND/AIM: To assess the impact of vitamin D supplementation on genomic and metabolomic profiles and relate them to the individual's responsiveness to varying doses of vitamin D3 Patients and Methods: Healthy adults were given either 600, 4000 or 10,000 IUs vitamin D3/day for 6 months. Circulating parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], calcium, peripheral white blood cells broad gene expression and urine and serum metabolomic profiles were evaluated. RESULTS: There was a dose-dependent effect of vitamin D supplementation on serum 25(OH)D, PTH and broad gene expression. Serum calcium levels remained normal for all study subjects and no untoward toxicity was observed. The metabolomic profiles were related to the genomic expression analysis. There were significant inter-individual effects on gene expression and metabolomic profile in response to the same dose of vitamin D3 supplementation, despite similar changes in 25(OH)D and PTH concentrations. CONCLUSION: These results may help explain the variability observed in clinical trials regarding vitamin D's non-calcemic health benefits.


Assuntos
Suplementos Nutricionais , Genômica , Metabolômica , Vitamina D/farmacologia , Adulto , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Hormônio Paratireóideo/sangue , Análise de Componente Principal , Mapas de Interação de Proteínas/efeitos dos fármacos , Vitamina D/análogos & derivados , Vitamina D/sangue
15.
Anticancer Res ; 40(1): 545-550, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892610

RESUMO

BACKGROUND/AIM: Many studies have shown an antiproliferative, anti-inflammatory, anti-angiogenetic, and apoptosis-inducing effect of Vitamin D. A vitamin D deficiency has been associated with an increased risk for different types of cancer. This study examined vitamin D 25(OH)D levels in gynaecological cancers in comparison with benign gynaecological diseases. PATIENTS AND METHODS: Serum 25(OH)D levels in 688 gynaecological patients (488 with malignant, 200 with a benign gynaecological disease) were assayed between 2009 and 2015 using an electrochemiluminescence immunoassay. RESULTS: In total, the 25(OH)D levels in cancer patients were lower, but not significantly lower than those in cancer-free patients. Significant results were shown regarding seasonal effects for patients with breast-, endometrial and ovarian cancer. No significant effects occurred with regard to menopause status, nicotine, or grade in relation to 25(OH)D levels. CONCLUSION: 25(OH)D levels seem to influence gynaecological cancers.


Assuntos
Doenças dos Genitais Femininos/sangue , Vitamina D/análogos & derivados , Fatores Etários , Feminino , Humanos , Menopausa/sangue , Estações do Ano , Vitamina D/sangue
16.
Ann Otol Rhinol Laryngol ; 129(1): 70-77, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31510765

RESUMO

OBJECTIVE: Prediction and early intervention for hypocalcemia following parathyroidectomy and total thyroidectomy can decrease hospital cost and prevent severe hypocalcemia-related complications. This study aims to predict the severity of hypocalcemia after parathyroidectomy or thyroidectomy and to stratify patients into groups with different levels of risk for developing severe hypocalcemia, so that higher risk patients may be monitored more closely and receive earlier interventions. METHODS: This was a retrospective cohort study of 100 patients with primary hyperparathyroidism who underwent parathyroidectomy as the primary treatment modality at a tertiary care hospital. Clinical information, including demographic information, perioperative PTH and calcium levels, vitamin D levels, weight of the pathologic glands removed, gland pathology, and re-admission rates, were retrieved. Statistical analysis was performed to analyze the association between collected variables and percentage of calcium drop following parathyroidectomy with statistical significant set at P-values <0.05. RESULTS: Age, sex, and vitamin D level provided very minimal information to quantify risks of postoperative hypocalcemia. The percentage of decrease from preoperative PTH level to the lowest PTH level after the removal of the abnormal gland(s) is the most significant predicting factor for the severity of postoperative hypocalcemia. There is a mathematic regressional correlation between them. A formula was generated to quantify this linear relationship between them, and the nadir calcium can be calculated as Canadir=Capreop*[1-0.35*(PTHpreop-PTHintraop)2PTHpreop2], where Canadir = the lowest postoperative calcium level, and PTHintraop = PTH level 15 minutes after removal of the abnormal gland, with the value of R2 > 0.7. The formula has been tested primarily in our patient population with good reliability. CONCLUSIONS: The highest preoperative, lowest postoperative, and change in PTH level can help us reliably calculate the trend of postoperative calcium level. Decision to pursue early interventions can be made based on the calculated result from the formula we obtained.


Assuntos
Hiperparatireoidismo Primário/cirurgia , Hipocalcemia/epidemiologia , Paratireoidectomia , Complicações Pós-Operatórias/epidemiologia , Adenoma/sangue , Adenoma/patologia , Adenoma/cirurgia , Adulto , Fatores Etários , Feminino , Humanos , Hiperparatireoidismo Primário/sangue , Hipocalcemia/sangue , Hipocalcemia/terapia , Período Intraoperatório , Magnésio/sangue , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/sangue , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/cirurgia , Complicações Pós-Operatórias/sangue , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Tireoidectomia , Carga Tumoral , Vitamina D/sangue
17.
Gut ; 69(1): 103-111, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31023832

RESUMO

OBJECTIVE: We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-reactive protein (CRP) level. We investigated the relationship between circulating vitamin D level and CRC survival. DESIGN: We sequentially sampled 92 patients undergoing CRC resection, and measured plasma 25OHD and CRP. For survival analyses, we assayed 25OHD and CRP in two temporally distinct CRC patient cohorts (n=2006, n=2100) and investigated the association between survival outcome, circulating vitamin D and systemic inflammatory response. RESULTS: Serial sampling revealed a postoperative fall (mean 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1-2). CRP peaked 3-5 days postoperatively (143.1 mg/L; p=1.4e-12), yet the postoperative fall in 25OHD was independent of CRP. In cohort analyses, 25OHD was lower in the 12 months following operation (mean=48.8 nmol/L) than preoperatively (54.8 nmol/L; p=1.2e-5) recovering after 24 months (52.2 nmol/L; p=0.002). Survival analysis in American Joint Committee on Cancer stages I-III demonstrated associations between 25OHD tertile and CRC mortality (HR=0.69; 95% CI 0.46 to 0.91) and all-cause mortality (HR=0.68; 95% CI 0.50 to 0.85), and was independent of CRP. We observed interaction effects between plasma 25OHD and rs11568820 genotype (functional VDR polymorphism) with a strong protective effect of higher 25OHD only in patients with GG genotype (HR=0.51; 95% CI 0.21 to 0.81). We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 25OHD with clinically useful predictive performance (area under the curve 0.77). CONCLUSIONS: CRC surgery induces a fall in circulating 25OHD. Plasma 25OHD level is a prognostic biomarker with low 25OHD associated with poorer survival, particularly in those with rs11568820 GG genotype. A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/cirurgia , Vitamina D/análogos & derivados , Idoso , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Receptores de Calcitriol/genética , Análise de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/sangue , Vitamina D/sangue
18.
Food Chem ; 305: 125475, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31518841

RESUMO

Pea protein-stabilized nanoemulsions were prepared to encapsulate vitamin D with the aim to develop novel non-dairy functional foods for vitamin D fortifications. Homogenization conditions of 20 kpsi and two homogenization cycles were identified as optimal conditions for producing stable nanoemulsions. The nanoemulsions exhibited controllable sizes (170-350 nm), good stability with zeta-potential of -25 mV, and high vitamin encapsulation efficiency (94-96%). Cellular uptake efficiency of small sized nanoemulsions (233 nm) was ~2.5 times higher than large sized nanoemulsions (350 nm). Interestingly, protein-based nanoemulsions exhibited significantly higher cellular uptake than emulsions prepared using a combination of protein and lecithin. The vitamin D transport efficiency across Caco-2 cells for small sized nanoemulsions (233 nm) was ~5.3 times greater than free vitamin D suspension. This research demonstrated that pea protein can be used as an effective emulsifier for preparing food nanoemulsions, which may enhance vitamin D bioavailability and improve vitamin deficiency status in aged population.


Assuntos
Emulsões/química , Nanoestruturas/química , Proteínas de Ervilha/química , Vitamina D/química , Células CACO-2 , Sobrevivência Celular , Emulsificantes/química , Humanos , Lecitinas/química , Nanoestruturas/toxicidade , Tamanho da Partícula , Pressão , Estabilidade Proteica , Vitamina D/metabolismo
19.
N Engl J Med ; 381(26): 2529-2540, 2019 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-31826336

RESUMO

BACKGROUND: Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality. RESULTS: A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P = 0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality. CONCLUSIONS: Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. (Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314.).


Assuntos
Colecalciferol/administração & dosagem , Estado Terminal/terapia , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/administração & dosagem , Adulto , Colecalciferol/efeitos adversos , Estado Terminal/mortalidade , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Falha de Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitaminas/efeitos adversos
20.
BMC Infect Dis ; 19(1): 1020, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791247

RESUMO

BACKGROUND: Vitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency. METHODS: We studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function. RESULTS: We demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver. CONCLUSIONS: Because FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.


Assuntos
Sepse/sangue , Sepse/complicações , Deficiência de Vitamina D/etiologia , Vitamina D/análogos & derivados , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Fator de Crescimento Insulin-Like I , Rim/efeitos dos fármacos , Testes de Função Renal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hormônio Paratireóideo/sangue , Sepse/fisiopatologia , Transdução de Sinais , Vitamina D/sangue , Vitamina D/metabolismo , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/fisiopatologia
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